The purpose of this project is to assess the regulation of glucose transporter gene expression by glucose, to identify the CCAAT/enhancer-binding proteins (C/EBP) implicated in the control of glucose transporter genes, and to test whether the nonoxidative branch of the pentose phosphate pathway might be critical for glucose-mediated metabolic gene expression. Fully-differentiated 3T3-L1 adipocytes in culture were subjected to four experimental conditions: elevated glucose feeding (25mM), glucose deprivation, use of non-metabolized glucose analogs, and xylitol. Northern blot analysis were conducted to determine the level of expression of various metabolic regulation genes. A coordinate regulation of C/EBPalpha and GLUT-4 mRNA levels was observed in all the culture conditions tested. In contrast, C/EBPa and GLUT-1 expression changed little over the course of the experiments while gadd153 gene was induced to high level in response to glucose starvation. It appears that phosphorylation of glucose to glucose-6-phosphate is indispensable for its transcriptional action on C/EBP and GLUT-4 genes. Evidence that the non-oxidative branch of the pentose phosphate pathway is involved in glucose-mediated regulation of gene expression is presented.